CROI 2013: All-Oral Regimens Work in HCV

ATLANTA – All-oral regimens under investigation for hepatitis C virus (HCV) were able to cure up to 95% of patients who had never been treated for the virus, a researcher said here.

But in combined 48-week data from two small clinical trials, only 47% of people who had previously had unsuccessful HCV therapy were cured, according to Eric Lawitz, MD, of the University of Texas Health Science Center in San Antonio.

On the other hand, treatment only lasted 12 weeks, the regimens were well-tolerated, and the handful of relapses took place soon after the end of therapy, Lawitz reported at the Conference on Retroviruses and Opportunistic Infections.

The key element of the trials – which actually tested two slightly different 4-drug regimens – was that patients were not given pegylated interferon, a backbone of standard HCV therapy that is difficult to tolerate and has dangerous side effects.

“We’re in a state of paradigm shift,” Lawitz told reporters before presenting the data, “in transition from interferon to the era of DAAs” – direct-acting agents that target HCV directly, rather than boosting the immune system, as interferon does.

His analysis looked at outcomes after treatment with regimens based on ribavirin and ABT-450, an NS3/4A protease inhibitor that is co-administered with ritonavir (Norvir). The drugs were combined with one of two non-nucleoside inhibitors of the HCV NS5B polymerase, ABT-072 or ABT-333.

The initial trial included 11 treatment-naïve patients with genotype 1 HCV, who were given 12 weeks of therapy with ribavirin, ABT-450/ribavirin, and ABT-072.

The second trial substituted ABT-333 for ABT-072 and had three cohorts – two with treatment-naïve patients who got different doses of ABT-333 (150 or 250 milligrams daily), and one with people who had previously failed interferon-based therapy, who also got the lower dose of ABT-333.

The primary endpoint was the 24-week sustained virologic response (SVR24) — the proportion of patients with undetectable virus 24 weeks after the end of therapy – that is usually regarded as a cure.

In the first trial, Lawitz reported that 91% of the patients reached the SVR24. In the second, the two treatment-naïve cohorts had SVR24 rates of 95% and 86%, while just 47% of those who had previously failed therapy before reached the milestone.

The IL28B polymorphism, which has variants that confer a greater risk of failing therapy, had no effect, Lawitz reported. Of the eight patients who relapsed, only two were among the treatment-naïve group and only one relapsed more than 12 weeks after the end of therapy, he reported.

There were no deaths or serious adverse events, he said, although one adverse event – an asymptomatic elevation in liver enzymes without any increase in bilirubin — led to premature discontinuation by a treatment-naïve patient. The liver enzymes returned to normal after the drugs were stopped.

One implication of the study might be that treating sicker patients will require more drugs or more time than treating people with less severe disease, commented Juergen Rockstroh, MD, of the University of Bonn, who was not involved in the study but who moderated the session at which it was presented.

“For easy-to-treat patients, two drugs (and ribavirin) will be just fine,” he told MedPage Today. But in the previous null responders, he noted, less than half of the patients were cured.

“This is really saying that we’re going to have interferon-free treatment for basically everyone who’s treatment-naïve,” Rockstroh said. What Lawitz’s data suggest, he added, is that a more aggressive strategy will be needed for everyone else.